{
  "abstract": "Pulmonary tuberculosis (TB), caused by lung infection with Mycobacterium tuberculosis (Mtb), often manifests both alveolar pneumonia and aggregation of immune cells containing Mtb, termed granulomas, within the same lung. Here, we integrate spatial transcriptomics, single-cell RNA sequencing, high-resolution imaging, and functional assays of lung biopsies from four men with pulmonary TB to compare alveolar pneumonia with adjacent granulomas. We find that alveolar TB pneumonia is enriched for TREM2⁺ lipid-laden macrophages characterized by increased lipid metabolism gene expression, reduced T cell infiltration, attenuated antimicrobial gene expression, and abundant Mtb transcripts and antigens. By contrast, neighboring granulomas exhibit organized lymphoid architecture and robust antimicrobial programs. In vitro, Mtb lipids induce TREM2 expression, activate TREM2-DAP12 signaling, and promote lipid droplet accumulation in primary human monocyte-derived macrophages (MDM). Furthermore, TREM2⁺ MDMs are more susceptible to in vitro Mtb infection. When treating MDMs with 1,25-dihydroxyvitamin D₃, which induces antimicrobial macrophage programs, TREM2⁺ MDM numbers, lipid droplet abundance and Mtb viability are decreased. Thus, we propose a spatially localized, alveolar pneumonia-intrinsic TREM2⁺ macrophage program that potentially contributes to Mtb persistence in pulmonary TB infection in humans.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.",
    "Laboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia.",
    "Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA, USA.",
    "Northwestern University, Chicago, IL, USA.",
    "Bruker Spatial Biology, Bothell, WA, USA.",
    "Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.",
    "Africa Health Research Institute, Durban, South Africa.",
    "Department of Forensic and Legal Medicine, Walter Sisulu University, Mthatha, South Africa.",
    "Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.",
    "Department of Pathology, Charles Nicolle Hospital, Tunis, Tunisia; LR23ES02, Faculté de Médecine de Tunis, Université de Tunis El Manar, Tunis, Tunisia.",
    "Department of Microbiology, Immunology and Infectious Diseases, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.",
    "Department of Pathology & Immunology, Washington University in St. Louis, St. Louis, MO, USA.",
    "Department of Microbiology, University of Alabama, Birmingham, USA.",
    "Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.",
    "Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.",
    "Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD, USA.",
    "Massachusetts Institute of Technology, Cambridge, MA, USA.",
    "Harvard T.H. Chan School of Public Health, Boston, MA, USA.",
    "Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. rmodlin@mednet.ucla.edu.",
    "Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. rmodlin@mednet.ucla.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 33,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rosane M B Teles",
      "orcid": "0000-0003-2908-3244"
    },
    {
      "affs": [
        1
      ],
      "name": "Chaouki Benabdessalem",
      "orcid": "0000-0001-7309-6814"
    },
    {
      "affs": [
        2
      ],
      "name": "Jonathan Perrie"
    },
    {
      "affs": [
        3
      ],
      "name": "Cenfu Wei",
      "orcid": "0000-0003-3368-4974"
    },
    {
      "affs": [
        0
      ],
      "name": "Julie West",
      "orcid": "0009-0004-6089-8948"
    },
    {
      "affs": [
        0
      ],
      "name": "Bruno J de Andrade Silva"
    },
    {
      "affs": [
        0
      ],
      "name": "Priscila R Andrade"
    },
    {
      "affs": [
        0
      ],
      "name": "Lilah A Mansky"
    },
    {
      "affs": [
        4
      ],
      "name": "Prajan Divaka"
    },
    {
      "affs": [
        5
      ],
      "name": "Linda Fischbacher"
    },
    {
      "affs": [
        0
      ],
      "name": "Karen Lam",
      "orcid": "0000-0003-4635-7008"
    },
    {
      "affs": [
        0
      ],
      "name": "Feiyang Ma",
      "orcid": "0000-0002-6260-0787"
    },
    {
      "affs": [
        2
      ],
      "name": "Yiqian Gu",
      "orcid": "0009-0000-9131-6278"
    },
    {
      "affs": [
        0
      ],
      "name": "Kimia Rategh"
    },
    {
      "affs": [
        0
      ],
      "name": "Madeline Brown"
    },
    {
      "affs": [
        0
      ],
      "name": "Aparna Pillai"
    },
    {
      "affs": [
        6
      ],
      "name": "Kapongo Lumamba"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Threnesan Naidoo"
    },
    {
      "affs": [
        8
      ],
      "name": "Samuel M French",
      "orcid": "0000-0002-7611-881X"
    },
    {
      "affs": [
        9
      ],
      "name": "Emna Romdhane"
    },
    {
      "affs": [
        1,
        10
      ],
      "name": "Mohamed-Ridha Barbouche"
    },
    {
      "affs": [
        11
      ],
      "name": "Eynav Klechevsky",
      "orcid": "0000-0001-6121-1571"
    },
    {
      "affs": [
        11
      ],
      "name": "Marco Colonna",
      "orcid": "0000-0001-5222-4987"
    },
    {
      "affs": [
        6,
        7,
        12
      ],
      "name": "Adrie J C Steyn",
      "orcid": "0000-0001-9177-8827"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Steven J Bensinger",
      "orcid": "0000-0002-9657-4206"
    },
    {
      "affs": [
        15
      ],
      "name": "Daniel L Barber",
      "orcid": "0000-0001-7008-7509"
    },
    {
      "affs": [
        9
      ],
      "name": "Soumaya Rammeh",
      "orcid": "0000-0003-0366-4630"
    },
    {
      "affs": [
        3
      ],
      "name": "Parambir S Dulai",
      "orcid": "0000-0002-9514-2321"
    },
    {
      "affs": [
        16
      ],
      "name": "Bryan D Bryson",
      "orcid": "0000-0003-1716-6712"
    },
    {
      "affs": [
        2
      ],
      "name": "Matteo Pellegrini",
      "orcid": "0000-0001-9355-9564"
    },
    {
      "affs": [
        5
      ],
      "name": "John T Belisle"
    },
    {
      "affs": [
        17
      ],
      "name": "Barry R Bloom"
    },
    {
      "affs": [
        18,
        19
      ],
      "name": "Robert L Modlin",
      "orcid": "0000-0003-4720-031X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/235qgne12sm1b.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-76814-8",
  "fulltext_url": "https://europepmc.org/articles/PMC13669344",
  "id": "235qgne12sm1b",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42875426",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7203859366",
  "pdf_url": "https://europepmc.org/articles/PMC13669344?pdf=render",
  "pmcid": "PMC13669344",
  "pmid": "42875426",
  "published": "2026-08-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/235qgne12sm1b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:18Z",
      "native_id": "MED:42875426",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42875426"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Tuberculosis Research and Epidemiology",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Identification of a spatially organized TREM2-associated permissive macrophage niche in human pulmonary tuberculosis alveolar pneumonia.",
  "title_text": "Identification of a spatially organized TREM2-associated permissive macrophage niche in human pulmonary tuberculosis alveolar pneumonia.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:18Z",
  "url": "https://research.draconitic.com/paper/235qgne12sm1b",
  "venue": "Nature communications",
  "versions": []
}